The general objective is to identify and characterize antigenic variants of carcinoembryonic antigen (CEA) of the human digestive system, focusing upon those antigenic determinants unique to CEA and shared with colon carcinoma antigen III (CCA-III). Using molecular sieve chromatography and a radiometric immunoassay with affinity-purified antibodies to the CEA-unique, CCA-III-unique, and CEA-CCA-III common sites, the characterization of antigen species bearing these determinants is studied in plasma and tissue from normal individuals and patients with malignant and non-malignant gastrointestinal disease. A clearer definition of CEA variants based on heterogeneity in determinant expression would provide opportunities to evaluate these variants with regards to tissue specificity, response to therapy, patient survival, and cancer cell evolution.